8464 RESULTS
COMMENT The authors did a tremendous job in creating a broad resource. Isogenic FAD/control iPSCs will likely set a new standard in the cellular modelling of AD-related phenotypes, and the lines reported here hopefully will be readily made available to a broader ...
COMMENT The overexpression paradigm is less problematic for modeling tauopathy than for Aβ amyloidosis because limited proteolysis is not a prerequisite for physiological and pathological processing of tau protein. Overexpression of APP results in overproduction ...
COMMENT We appreciate the new comment from Dr. Kipnis and colleagues and their willingness to engage in discussion on this controversial topic. We also feel the need to clarify some of the statements that have been made by these authors in their comments to this ...
COMMENT This paper suggests that defects in GLT-1 (also known as EAAT2) in astrocytes lead to accumulation of synaptic glutamate, which causes hyperactivity, leading to excitotoxicity of and Ca2+ entry to neurons. Nearly two decades ago, our laboratory ...
COMMENT Pioneering work from several groups, most notably from Ralph Nixon and colleagues, identified dysfunction of the endolysosomal network in Alzheimer’s disease, and that this was due to abnormal processing of APP. This exciting study is an important ...
COMMENT This is a very impressive and exhaustive study by the Tessier-Lavigne lab showing that APP β-CTFs, but not Aβ, drives endosomal enlargement in human neurons from patients with familial AD (FAD). Using more than fifteen isogenic iPSC lines, the authors ...
COMMENT Recent failures of Aβ-centric clinical trials highlight the need for investigating early cellular phenotypes that cause dysfunction upstream of amyloid and tau pathology in Alzheimer’s disease. Endosome enlargement is an early cytopathology in AD, and ...
COMMENT Induced pluripotent stem cell (iPSC)-derived cell types are widely used as physiologically-relevant models of human neurodegenerative disease, but challenges still remain around the inherent variability driven largely by differing genetic backgrounds. A ...
COMMENT This paper reproduces findings in human iPSC-derived neurons that others made decades ago in much simpler cell systems. These cell lines are therefore a nice and important resource for future research, but I would have expected a balanced discussion and ...
COMMENT This report on CRISPR-modified IPSC neurons expressing diverse APP and PSEN1 FAD mutations is a technical tour de force. It is a welcome confirmation of our previous findings on neurons in AD, FAD, and Down’s Sydrome (DS) brains and human DS fibroblasts, ...
COMMENT This is an interesting and comprehensive whole-transcriptome study of APOE4 and Alzheimer’s disease (AD), using human iPSC-derived brain cells, mouse brain cells, and cell-type deconvoluted transcriptomic data from postmortem AD brains. An important ...
COMMENT This is an exciting study demonstrating that APOE4 is associated with dysregulation of cholesterol homeostasis in human but not mouse astrocytes and microglia. Although such an association was implicated in previous studies, including those addressing ...
COMMENT This new story is noteworthy not only for the findings but also for the lack of adequate exposition [or the significance] of the downstream sequels to a neuron ‘driven’ into an “…hyperactive frenzy…”. One of the longstanding challenges for all the major ...
COMMENT This paper describes impressive experimentation with convincing results, though I would be interested in seeing more discussion of chronic glutamate toxicity in AD. Before investing further in therapeutic strategies targeting reduction of Aβ-oligomers, ...
COMMENT This is an interesting follow-up from the authors’ previous study showing the role of PU.1 in microglial AD risk gene networks. Now the authors extend their analyses to functional variants in monocyte and macrophage enhancers that alter the expression of ...
